Azaribine (2', 3', 5'-triacetate-6-azauridine) has been found to be effective in oral dosage form for the treatment of psoriasis, psoriatic arthritis, polycythemia vera, mycosis fungoides, and choriocarcinoma. However, a severe side effect, namely life-threatening thromboembolic episodes of up to four percent of the patients treated, caused the recall of the drug by the Food and Drug Administration (FDA).
It has been discovered in man, as well as in rabbits, that oral administration of the azaribine resulted in severe pyridoxal phosphate deficiency and abnormally high levels of homocysteine, which are presumed to be related to the thrombogenic side-effects of this drug. It has also been shown that, in rabbits, severe pyridoxal phosphate deficiency, as well as the homocysteinemia, can be prevented or at least reduced by the concomitant administration of pyridoxine.
The mechanism by which azaribine interferes with pyridoxal phosphate is unknown, but has been attributed to an interference with pyridoxal phosphate coenzymes essential to the proper metabolism of the accumulated amino acids. It has been shown that homocysteine accumulates in pigs fed a vitamin B.sub.6 -deficient diet. It has been suggested that a catabolite of 6-azauridine, the active drug substance formed by the hydrolysis of azaribine after its absorption, results through cleavage of the triazine ring of 6-azauridine. This catabolite has been postulated to be a hydrazine or semicarbazide derivative which can readily and rapidly react with pyridoxal phosphate, resulting in severe deficiency.